S-antigen (S-Ag) induced experimental autoimmune uveoretinitis (EAU) is a recognized model for investigating the immunopathological mechanisms possibly involved in certain human uveitic diseases. The purpose of this project was to identify and isolate pathogenic and antigenic epitopes present on this unique autoantigen. Cyanogen bromide cleavage and S. aureus V8 digestion were utilized to produce fragments of the S-Ag. These were then characterized and isolated by electrophoretic and immunoblotting methods. Identification of antigenic epitopes was made possible using recently developed monoclonal antibodies specific for determinants present on the S-Ag molecule. Many of the fragments were also shown to contain antigenic determinants reactive to both monoclonal and polyclonal antibody probes. Pathogenic epitopes present of the isolated peptides were tested using the rat EAU model. Fragments of approximate molecular sizes of 45kD, 25kD and 14kD were found to be uveitogenic in microgram amounts.